Functional brain network (FBN) has been becoming an increasingly important way to model the statistical dependence among neural time courses of brain, and provides effective imaging biomarkers for diagnosis of some neurological or psychological disorders. Currently, Pearson’s Correlation (PC) is the simplest and most widely-used method in constructing FBNs. Despite its advantages in statistical meaning and calculated performance, the PC tends to result in a FBN with dense connections. Therefore, in practice, the PC-based FBN needs to be sparsified by removing weak (potential noisy) connections. However, such a scheme depends on a hard-threshold without enough flexibility. Different from this traditional strategy, in this paper, we propose a new approach for estimating FBNs by remodelling PC as an optimization problem, which provides a way to incorporate biological/physical priors into the FBNs. In particular, we introduce an L1-norm regularizer into the optimization model for obtaining a sparse solution. Compared with the hard-threshold scheme, the proposed framework gives an elegant mathematical formulation for sparsifying PC-based networks. More importantly, it provides a platform to encode other biological/physical priors into the PC-based FBNs. To further illustrate the flexibility of the proposed method, we extend the model to a weighted counterpart for learning both sparse and scale-free networks, and then conduct experiments to identify autism spectrum disorders (ASD) from normal controls (NC) based on the constructed FBNs. Consequently, we achieved an 81.52% classification accuracy which outperforms the baseline and state-of-the-art methods.

Mild cognitive impairment (MCI) is often considered a critical time window for predicting early conversion to Alzheimer’s disease (AD). Brain functional connectome data (i.e., functional connections, global and nodal graph metrics) based on resting-state functional magnetic resonance imaging (rs-fMRI) provides numerous information about brain networks and has been used to discriminate normal controls (NCs) from subjects with MCI. In this paper, Student’s t-tests and group-least absolute shrinkage and selection operator (group-LASSO) were used to extract functional connections with significant differences and the most discriminative network nodes, respectively. Based on group-LASSO, the middle temporal, inferior temporal, lingual, posterior cingulate, and middle frontal gyri were the most predominant brain regions for nodal observation in MCI patients. Nodal graph metrics (within-module degree, participation coefficient, and degree centrality) showed the maximum discriminative ability. To effectively combine the multipattern information, we employed the multiple kernel learning support vector machine (MKL-SVM). Combined with functional connectome information, the MKL-SVM achieved a good classification performance (area under the receiving operating characteristic curve = 0.9728). Additionally, the altered brain connectome pattern revealed that functional connectivity was generally decreased in the whole-brain network, whereas graph theory topological attributes of some special nodes in the brain network were increased in MCI patients. Our findings demonstrate that optimal feature selection and combination of all connectome features (i.e., functional connections, global and nodal graph metrics) can achieve good performance in discriminating NCs from MCI subjects. Thus, the combination of functional connections and global and nodal graph metrics of brain networks can predict the occurrence of MCI and contribute to the early clinical diagnosis of AD.

Mild cognitive impairment (MCI) is an intermediate stage of brain cognitive decline, associated with increasing risk of developing Alzheimer's disease (AD). It is believed that early treatment of MCI could slow down the progression of AD, and functional brain network (FBN) could provide potential imaging biomarkers for MCI diagnosis and response to treatment. However, there are still some challenges to estimate a “good” FBN, particularly due to the poor quality and limited quantity of functional magnetic resonance imaging (fMRI) data from the target domain (i.e., MCI study). Inspired by the idea of transfer learning, we attempt to transfer information in high-quality data from source domain (e.g., human connectome project in this paper) into the target domain towards a better FBN estimation, and propose a novel method, namely NERTL (Network Estimation via Regularized Transfer Learning). Specifically, we first construct a high-quality network “template” based on the source data, and then use the template to guide or constrain the target of FBN estimation by a weighted l1-norm regularizer. Finally, we conduct experiments to identify subjects with MCI from normal controls (NCs) based on the estimated FBNs. Despite its simplicity, our proposed method is more effective than the baseline methods in modeling discriminative FBNs, as demonstrated by the superior MCI classification accuracy of 82.4% and the area under curve (AUC) of 0.910.

Functional connectivity (FC) network has been becoming an increasingly useful tool for understanding the cerebral working mechanism and mining sensitive biomarkers for neural/mental disease diagnosis. Currently, Pearson's Correlation (PC) is the simplest and most commonly used scheme in FC estimation. Despite its empirical effectiveness, PC only encodes the low-order (i.e., second-order) statistics by calculating the pairwise correlations between network nodes (brain regions), which fails to capture the high-order information involved in FC (e.g., the correlations among different edges in a network). To address this issue, we propose a novel FC estimation method based on Matrix Variate Normal Distribution (MVND), which can capture both low- and high-order correlations simultaneously with a clear mathematical interpretability. Specifically, we first generate a set of BOLD subseries by the sliding window scheme, and for each subseries we construct a temporal FC network by PC. Then, we employ the constructed FC networks as samples to estimate the final low- and high-order FC networks by maximizing the likelihood of MVND. To illustrate the effectiveness of the proposed method, we conduct experiments to identify subjects with Mild Cognitive Impairment (MCI) from Normal Controls (NCs). Experimental results show that the fusion of low- and high-order FCs can generally help to improve the final classification performance, even though the high-order FC may contain less discriminative information than its low-order counterpart. Importantly, the proposed method for simultaneous estimation of low- and high-order FCs can achieve better classification performance than the two baseline methods, i.e., the original PC method and a recent high-order FC estimation method.

Functional brain network (FBN) is becoming an increasingly important measurement for exploring cerebral mechanisms and mining informative biomarkers that assist diagnosis of some neurodegenerative disorders. Despite its effectiveness to discover valuable hidden patterns in the human brain, the estimated FBNs are often heavily influenced by the quality of the observed data (e.g., blood oxygen level dependent signal series). In practice, a preprocessing pipeline is usually employed for improving data quality. With this in mind, some data points (volumes or time course in the time series) are still not clean enough, due to artifacts including spurious resting-state processes (head movement, mind-wandering). Therefore, not all volumes in the fMRI time series can contribute to the subsequent FBN estimation. To address this issue, we propose a novel FBN estimation method by introducing a latent variable as an indicator of the data quality, and develop an alternating optimization algorithm for jointly scrubbing the data and estimating FBN simultaneously. To further illustrate the effectiveness of the proposed method, we conduct experiments on two public datasets to identify subjects with mild cognitive impairment from normal controls based on the estimated FBNs, and achieve improved accuracies than the baseline methods.

¹⁸F‐Fluorodeoxyglucose positron emission tomography (¹⁸F‐FDG PET) is widely employed to reveal metabolic abnormalities linked to Parkinson's disease (PD) at a systemic level. However, the individual metabolic connectome details with PD based on ¹⁸F‐FDG PET remain largely unknown. To alleviate this issue, we derived a novel brain network estimation method for individual metabolic connectome, that is, Jensen‐Shannon Divergence Similarity Estimation (JSSE). Further, intergroup difference between the individual's metabolic brain network and its global/local graph metrics was analyzed to investigate the metabolic connectome's alterations. To further improve the PD diagnosis performance, multiple kernel support vector machine (MKSVM) is conducted for identifying PD from normal control (NC), which combines both topological metrics and connection. Resultantly, PD individuals showed higher nodal topological properties (including assortativity, modularity score, and characteristic path length) than NC individuals, whereas global efficiency and synchronization were lower. Moreover, 45 most significant connections were affected. Further, consensus connections in occipital, parietal, and frontal regions were decrease in PD while increase in subcortical, temporal, and prefrontal regions. The abnormal metabolic network measurements depicted an ideal classification in identifying PD of NC with an accuracy up to 91.84%. The JSSE method identified the individual‐level metabolic connectome of ¹⁸F‐FDG PET, providing more dimensional and systematic mechanism insights for PD.